Comparison of the therapeutic index of padsevonil and nine other antiepileptic drugs with different mechanisms of action determined in the mouse amygdala kindling model and rotarod test.
Other than padsevonil, brivaracetam, and valproate, the ED50 values—and, therefore, the therapeutic index of the other antiepileptic drugs—could not be calculated.
| Drug | Amygdala Kindling ED50 | MAD/Protection Against Seizuresa | MTD/Protection Against Seizuresa | Rotarod Test TD50 | Therapeutic Index |
|---|---|---|---|---|---|
| mg/kg | (mg/kg)/% | (mg/kg)/% | mg/kg | ||
| Padsevonil | 1.2 (0.4–3.4) | 1.4/60 | 13.9/100 | 12 (9–15) | 9.8 |
| Brivaracetam | 68 (39–118) | 134/90 | 212/91 | 195 (133–245) | 2.8 |
| Levetiracetam | — | 540/60 | 540/60 | 1389 (962–2041) | — |
| Valproate | 239 (169–338) | 250/56 | 400/89 | 298 (201–418) | 1.2 |
| Phenytoin | — | >70/0 | 70/0 | 129 (76–194) | — |
| Carbamazepine | — | 56/89 | 56/89 | 36 (27–48) | — |
| Lamotrigine | — | >56/33 | 56/33 | 20 (13–27) | — |
| Diazepam | — | 3/89 | 3/89 | 3 (2–4) | — |
| Topiramate | — | >300/25 | 300/25 | 249 (150–357) | — |
| Retigabine | — | 15/100 | 15/100 | 12 (8–18) | — |
MAD, minimally active dose, defined as the lowest dose providing statistically significant protection against focal to bilateral tonic-clonic seizures; MTD, maximal tested dose, defined as the highest dose tested in the amygdala kindling model;—, not calculated.
↵a Protection against focal to bilateral tonic-clonic seizures.